The proposed project is directed towards better defining the mechanisms underlying the production of anemia and thrombocytosis in neoplastic disorders. The studies dealing with the anemia of cancer will include: 1) isolation of erythropoiesis inhibitory factors from human plasma obtained from cancer patients with anemia; 2) establishment of short-term cultures of tumor cells and assays of their supernatants for erythropoiesis inhibitory activity; 3) co-cultivation of tumor cells with normal bone marrow to determine the importance of a tumor cell-erythroid progenitor cell relationship in the production of anemia. To gain an understanding of the production of thrombocytosis in patients with solid tumors and myeloproliferative disorders, the following studies are planned: 4) assay of peripheral blood and bone marrow from patients with solid tumors or myeloproliferative disorders associated with thrombocytosis for megakaryocytic colony forming units (CFU-M); 5) purification of CFU-M using immunologic surface markers; 6) determination of humoral and cellular factors important in the regulation of normal CFU-M and those from cancer patients with thrombocytosis; 7) cell cycle analysis of peripheral blood and bone marrow CFU-M; 8) cytogenetic analysis of megakaryocyte colonies produced by Ph1 chronic granulocytic leukemia bone marrow cells; 9) separation of megakaryocytes from bone marrow cells and determination of their DNA content; 10) cell cycle analysis of bone marrow megakaryocytes from patients with thrombocytosis associated with neoplastic disorders; 11) immunologic identification of megakaryoblastic leukemia.